Composite vitamin composition promoting gastrointestinal system motility

ABSTRACT

Disclosed are composite compositions of B vitamins and C vitamins and the use of same in the preparation of a drug or health food for treating and/or preventing gastrointestinal conditions diseases related to deficiency of the gastrointestinal system motility. The composition comprises a vitamin B composition or an analogue or a derivative thereof and a vitamin C or an analogue or a derivative thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is continuation of U.S. application Ser. No.16/462,510, filed on May 20, 2019, which is a U.S. National StageApplication under 35 U.S.C. § 371 of International Patent ApplicationNo. PCT/CN2017/109280, filed Nov. 3, 2017, which claims the benefit ofChinese Application No. 201611036830.5, filed Nov. 23, 2016, thedisclosure of each of which is incorporated by reference herein in itsentirety.

FIELD OF THE INVENTION

The present invention relates to a composition comprising B vitamins andC vitamins, in particular to a composition comprising B vitamins and Cvitamins for promoting motility of the gastrointestinal system. Thepresent composition is suitable for the prevention and/or treatment ofconditions or diseases associated with deficiencies of gastrointestinalmotility.

BACKGROUND OF THE INVENTION

Nowadays, the pressure of people's life is generally increasing, thepace of life is accelerating, and the competition is fiercer day by day.More and more patients are suffering from gastrointestinal disorders orgastrointestinal discomfort. The pathogeny thereof is extensive, and thesymptoms thereof are also different.

Gastrointestinal (GI) motility is a coordinated neuromuscular processthat transports nutrients through the digestive system. Impairedmotility of the gastrointestinal system can be involved ingastroesophageal reflux disease, gastroparesis (e.g., diabetic andpostsurgical gastroparesis), irritable bowel syndrome (IBS), ileus, andconstipation (e.g., functional or drug-induced constipation), and is oneof the largest health care burdens of industrialized nations. In view ofthe above, a way to effectively stimulate motility of thegastrointestinal system is highly desirable and would be an advance inthe art.

Functional dyspepsia and chronic gastritis often have such symptoms asabdominal fullness, upper abdominal pain, nausea, anorexia and so on. Animportant reason for this kind of symptoms is delayed gastric emptyingcaused by gastrointestinal motility disorders. And gastrointestinalmotility disorders tend to cause IBS. Currently, drugs for treatment ofgastrointestinal motility include metoclopramide, domperidone anditopride.

In the past, there were many kinds of drugs for treatment ofgastrointestinal diseases, but few drugs have good curative effects andno side effects, and drugs or health care products with long-term healthcare effects as well as improving gastrointestinal function, promotinggastrointestinal motility and relieving gastrointestinal discomfortsymptoms are even rare.

As mentioned above, (1) metoclopramide as a dopamine receptor blockingdrug with strong central anti-vomiting and gastrointestinal tractexcitement effects, can inhibit the relaxation of gastric smooth muscle,increase the response of gastrointestinal smooth muscle to cholinergic,accelerate gastric emptying, and increase the activity of the gastricantrum. In addition, the drug also has the function of stimulating therelease of prolactin. The side effects of Metoclopramide commonlyinclude lethargy, irritability, fatigue, and weakness. Moreover,high-dose or long-term use of the drug may block the dopamine receptor,showing the symptoms of Parkinson's disease. (2) Domperidone as aperipheral dopamine receptor antagonist can promote uppergastrointestinal peristalsis and tension recovery, facilitate gastricemptying, increase the movement of gastric antrum and duodenum,coordinate pyloric contraction, and enhance esophageal peristalsis andthe tension of the lower esophageal sphincter. Because of its poorpenetration into the blood brain barrier, domperidone almost has noantagonistic effect on the dopamine receptor in the brain. It isreported abroad that its high-dose intravenous injection may causeseizures (there is no this preparation in China). This drug, however, isa powerful prolactin-releasing drug which may cause menstrual disorders.(3) Itopride has dual effects of dopamine receptor blockade andacetylcholinesterase inhibition. It can enhance the movement of stomachand duodenum and facilitate gastric emptying by stimulating the releaseof endogenous acetylcholine and inhibiting the hydrolysis thereof. Italso has a moderate anti-vomiting effect. The elderly or aged patientsshould use this drug with caution.

B vitamins are all water soluble, most of which are coenzymes, takingpart in the in vivo metabolism of sugar, protein and fat.

Vitamin B1 (thiamine) can promote gastrointestinal peristalsis andincrease appetite. Vitamin B1 can inhibit the activity of cholinesteraseto hydrolyze acetylcholine. Lack of vitamin B1 may increase the activityof cholinesterase and accelerate the hydrolysis of acetylcholine.Acetylcholine is an important neurotransmitter and its deficiency canlead to nerve conduction disorders, especially affecting the nerveconduction at the gastrointestinal tract and gland, and lead to slowgastrointestinal peristalsis, abdominal distension, diminished digestiveglandular secretion, and appetite decrease.

Vitamin B2 constitutes many important coenzymes in the flavoproteins. Itcan be converted into flavin mononucleotide (FMN) and flavin adeninedinucleotide (FAD), both of which are important coenzymes in the tissuerespiration, function to transfer hydrogen in the enzyme system, andparticipate in the metabolism of sugar, protein and fat, and canmaintain normal visual function. Furthermore, Vitamin B2 can activateVitamin B6 and convert tryptophan into niacin, and may be related tomaintaining the integrity of red blood cells. It can maintain andimprove the health of epithelial tissue, such as the gastrointestinalmucosal tissue. When the human body lacks B2, especially in severedeficiency status, the mucosal layer of human body cavity will haveproblems that cause mucosal lesions, and this can enhance thecarcinogenic effect of chemical carcinogens. Vitamin B2 can thus preventcancer.

Vitamin B3 (niacin) constitutes a coenzyme of dehydrogenase in the body.Vitamin B3, as the most requisite amount of B vitamins of the humanbody, not only keeps health of the digestive system, but also alleviatesgastrointestinal disorders. Niacin is converted into nicotinamide in thehuman body. Nicotinamide is a component of coenzyme I and coenzyme IIand participates in the in vivo lipid metabolism, oxidation process oftissue respiration, and the anaerobic decomposition of carbohydrates. Itcan keep the health of the digestive system, relieve gastrointestinaldisorders, and effectively relieve the symptoms of constipation. Itsdeficiency can lead to angular cheilitis, glossitis, diarrhea, and soon. Diarrhea is a typical symptom of this disease. Constipation oftenoccurs in its early days. Then it is often accompanied by diarrheabecause of enteritis and the atrophy of the intestinal wall, digestivegland, intestinal wall and mucosa, and intestinal villus. The stool iswatery or pasty, with large quantities and a lot of stink and sometimeswith blood. Tenesmus may happen when the lesion is near the anus.Diarrhea is often severe and refractory and can be combined withabsorption disorders.

Vitamin B5 (pantothenic acid) has an active form of coenzyme A, is anacyl carrier in vivo, and participates in the metabolism of sugar, fat,and protein. They work synergistically to regulate metabolism, maintainskin and muscle health, enhance the functions of the immune system andnervous system, and promote cell growth and division (includingpromotion of production of red blood cells and prevention of anemia).The lack of vitamin B5 may lead to the symptoms including anepithymia,dyspepsia, and being susceptible to duodenal ulcer.

Vitamin B6 comprises pyridoxine, pyridoxal and pyridoxamine, which canbe transformed to one another. It can react with ATP in vivo via anenzyme and then be transformed into a coenzyme of a variety of enzymeshaving physiological activity, thereby participating in variousmetabolic functions of amino acids and fats. Combined with vitamin B1,it has a strong analgesic effect. Vitamin B12 can enhance the analgesiceffect by the combination of the above two, and relieve the pain causedby peripheral nerve disease and spinal cord disease. Studies havereported that the intravenous drip of vitamin B6 mixed with azithromycincan reduce side effects of azithromycin on the gastrointestinal tract.Its main targets are blood, muscle, nerves, skin, etc. Its functions arethe synthesis of antibodies, production of gastric acid in the digestivesystem, utilization of fat and protein (which should be supplementedespecially on a diet), and the maintenance of the sodium/potassiumbalance (stabilization of the nervous system). Lack of vitamin B6damages cells and affect humoral immunity. Feeding of vitamin B6 canimprove immunity, reduce carcinogens in the body, and has a certainanticancer effect.

Vitamin B7, also known as vitamin H, biotin, and coenzyme R, is involvedin the metabolism of fatty acids and carbohydrates in the body,promoting protein synthesis. It also involved in the metabolism ofvitamin B12, folic acid, and pantothenic acid. It can promote ureasynthesis and excretion, enhance the body's immune response andresistance to infection, stabilize the lysosomal membrane of normaltissues, maintain the body's humoral immunity and cellular immunity,affect the secretion of a series of cytokines, improve the body's immunefunction, and reduce the symptoms of perianal eczema and itching. Thebiotin side chain carboxyl group can be linked to the lysine residues ofthe enzyme via an amide bond. Biotin is a carboxyl carrier and is alsoinvolved in the metabolism of vitamin B12, folic acid, and pantothenicacid.

Vitamin B9 (folic acid) belongs to water-soluble B vitamins consistingof pteridine, p-aminobenzoic acid, and glutamic acid residues. The drugis absorbed by the intestinal tract and then passes through the portalvein into the liver, where it is converted into an activetetrahydrofolic acid under the action of the dihydrofolate reductase.Tetrahydrofolic acid is the carrier of “one carbon group” in the body.The “one carbon group” can be linked to the tetrahydrofolic acid at its5 or 10-position carbon atom, and is mainly involved in the synthesisand transformation of purine nucleotides and pyrimidine nucleotides. Themethyl group required for conversion of uracil nucleotides to thymidinenucleotides is derived from the methylene group provided bytetrahydrofolic acid bearing a “one carbon group”. As a result, folicacid deficiency can result in a “one carbon group” transfer barrier, anda difficult synthesis of thymidine nucleotide, thereby affecting DNAsynthesis and slowing down the rate of cell division, that is, the cellcycle will only stay in the G1 phase and the S and G2 phases will berelatively prolonged. The above changes will affect not onlyhematopoietic cells (causing the megaloblastic anemia) but also thesomatic cells (especially the digestive tract mucosal cells). Folic aciddeficiency can lead to B1 absorption disorders. The health benefits offolic acid for women are widely noted in the medical community, andpregnant and lactating women should be supplemented with folic acid.Besides, it can be used to prevent rectal cancer and heart disease. Ithas also been found to prevent free radicals from destroyingchromosomes. Humans with deficient folic acid may suffer frommegaloblastic anemia and leukopenia.

Deoxyadenosine cobalamin is the main existing form of vitamin B12 in thebody and is a cobalt-containing red compound that is active only afterit is converted to methylcobalamin and coenzyme B12. Vitamin B12 andfolic acid play an important role in DNA synthesis. In addition, vitaminB12 also plays an important role in the maturation of red blood cellsand in the normal maintenance of the nervous system. It is oftenassociated with the role of folic acid. Folic acid has multiple coenzymeforms in the cell, and some studies have suggested that folic acid canintervene in the occurrence of gastrointestinal cancer and that folicacid can treat atrophic gastritis and improve gastric mucosal pathology.

Choline bitartrate has the effect of promoting the transformation ofphospholipids and accelerating the operation of fat, and has acholagogic effect; inositol can promote cell metabolism, promotedevelopment, and increase appetite. P-aminobenzoic acid (PABA) isactually a component of folic acid and it functions as a coenzyme in thebody. PABA works with folic acid to promote protein metabolism and bloodcell production.

Vitamin C, also known as ascorbic acid, is one of antioxidant vitamins.It participates in hydroxylation reaction in the body and is requiredfor the formation of bones, teeth, and the interstitial adhesions inconnective tissues and non-epithelial tissues. It can maintain thenormal function of the teeth, bones, and blood vessels, and increaseresistance to diseases. It is reported that vitamin C is deficient atdifferent levels in various populations. When the body has some smallproblems, people should promptly be supplemented with vitamins andminerals to improve nutrition deficiencies, especially the elderlyshould pay more attention. Vitamins have a preventive effect on manydiseases, many diseases may be more or less related to the lack ofvitamin C, and vitamin C can also be combined with many other drugs totreat some diseases. Vitamin C is an antioxidant that protects the bodyfrom the threat of free redicals. Vitamin C is also a coenzyme. Manystudies have shown that vitamin C can block the synthesis ofcarcinogenic N-nitroso compounds, prevent the formation of carcinogenicammonium nitrate in the salted, pickled, and smoked foods containingnitrite (bacon, sausage, and so on), and prevent cancer, especially ithas a better preventive effect on rectal cancer and colon cancer. At thesame time, it has the effect of softening the blood vessels of the anusand increasing the elasticity of the anus. VC is easily damaged by heator oxidants, especially light, trace heavy metals, and fluorescentsubstances can promote its oxidation, which makes VC be greatlyrestricted in application. Therefore, derivatives of vitamin C,including metal salts of VC, esters generated by VC with various acids,and compounds of VC and carbohydrates, etc., not only can get rid of theinstability nature of VC, but also can better exert the physiologicalfunction of VC. These derivatives include vitamin C (L-ascorbic acid),Sodium ascorbate (L-sodium ascorbate), magnesium ascorbyl phosphate,L-Ascorbate-polyphosphate, ascorbyl palmitate, ascorbin stearate,vitamin C and glucose compound, etc.

From the perspective of mechanism of action, vitamin B is an importantcoenzyme involved in energy metabolism of human body, and vitamin C canpromote the body's absorption of members of B vitamins. Multivitamin B Cis used to improve the energy metabolism of the human body and providemore energy for the gastrointestinal tract to improve the functionaldyspepsia caused by inadequate gastrointestinal motility. The mechanismfor the increase in energy metabolism includes assisting carbohydratesand fat in releasing energy, decomposing amino acids, and transportingnutrient-containing oxygen and energy throughout the body. MultivitaminBC will be likely to become a new drug or health food with higher safetyfor promoting the motility of gastrointestinal system, yet there is noevidence to date to prove the ability of vitamin B and vitamin C topromote the motility of the gastrointestinal system, especially thetherapeutic and regulatory effect of vitamin B and vitamin C on motilitydisorders of the gastrointestinal system in pathological state. Due tothe large number of family members of B vitamins and theirinterdependent relationship, component selection and compatibility ofthe B vitamins are very important for preparation of drugs or healthfood for the treatment or regulation of motility disorders of thegastrointestinal system.

DISCLOSURE OF THE INVENTION A. Summary of the Invention

The present invention relates to a method of stimulating the motility ofthe gastrointestinal system in a subject in need thereof, wherein saidsubject suffers from diseases (i.e., disorders, conditions, symptoms, ordrug- or surgery-induced dysfunction) of the gastrointestinal system.The method comprises administering to a subject in need thereof atherapeutically effective amount of a composition comprising B vitaminsand C vitamins. The vitamins referred to in this invention comprisetheir corresponding analogues or derivatives, for example, vitamin B1means thiamine and analogs or derivatives thereof, vitamin B2 denotesriboflavin and analogs or derivatives thereof; vitamin B3 refers tonicotinic acid and analogs or derivatives thereof; vitamin B5 meanspantothenic acid and analogs or derivatives thereof; vitamin B6 meanspyridoxine and analogs or derivatives thereof; vitamin B7 is biotin andanalogues or derivatives thereof; vitamin B9 means folic acid andanalogs or derivatives thereof; vitamin B12 means cyanocobalamine andanalogs or derivatives thereof; vitamin C means ascorbic acid andanalogs or derivatives thereof; and so on. In one preferred embodiment,the composition comprising B vitamins and C vitamins is a compositioncomprising vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3(nicotinic acid), vitamin B5 (pantothenic acid), vitamin B6, biotin, andvitamin C. In one more preferred embodiment, the composition comprisingB vitamins and C vitamins is a composition comprising vitamin B1(thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid),vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin, vitaminC, choline bitartrate, and inositol. In another more preferredembodiment, the composition comprising B vitamins and C vitamins is acomposition comprising vitamin B1 (thiamine), vitamin B2 (riboflavin),vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6, vitaminB12, folic acid, biotin, vitamin C, choline bitartrate, inositol, andp-aminobenzoic acid.

In another aspect, this invention provides a composition comprising aneffective amount of a combination of B vitamins and C vitamins, and apharmaceutically acceptable carrier. In one preferred embodiment, thecomposition comprises an effective amount of vitamin B1 (thiamine),vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenicacid), vitamin B6, biotin, and a pharmaceutically acceptable carrier. Inone more preferred embodiment, the composition comprises an effectiveamount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3(niacin), vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin,vitamin C, choline bitartrate, inositol, and a pharmaceuticallyacceptable carrier. In another more preferred embodiment, thecomposition comprises an effective amount of vitamin B1 (thiamine),vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenicacid), vitamin B6, vitamin B12, folic acid, biotin, vitamin C, cholinebitartrate, inositol, p-aminobenzoic acid, and a pharmaceuticallyacceptable carrier.

In yet another aspect, the present invention relates to a compositioncomprising an effective amount of a combination of B vitamins and Cvitamins, and an effective amount of drugs for treating and/orpreventing gastrointestinal diseases. In one preferred embodiment, thecomposition comprises an effective amount of vitamin B1 (thiamine),vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenicacid), vitamin B6, biotin, vitamin C, and an effective amount of drugsfor treating and/or preventing gastrointestinal diseases. In one morepreferred embodiment, the composition comprises an effective amount ofvitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin),vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin, vitaminC, choline bitartrate, inositol, and an effective amount of drugs fortreating and/or preventing gastrointestinal diseases. In another morepreferred embodiment, the composition comprises an effective amount ofvitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin),vitamin B5 (pantothenic acid), vitamin B6, vitamin B12, folic acid,biotin, vitamins C, choline bitartrate, inositol, p-aminobenzoic acid,and an effective amount of drugs for treating and/or preventinggastrointestinal diseases.

In still yet another aspect, the present invention relates to acomposition comprising an effective amount of a combination of Bvitamins and C vitamins, and an effective amount of other vitamincompounds. In one preferred embodiment, the composition comprises aneffective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin),vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6, biotin,vitamin C, and an effective amount of other vitamin compounds. In onemore preferred embodiment, the composition comprises an effective amountof vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin),vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin, vitaminC, choline bitartrate, inositol, and an effective amount of othervitamin compounds. In another more preferred embodiment, the compositioncomprises an effective amount of vitamin B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, vitamin B12, folic acid, biotin, vitamin C, cholinebitartrate, inositol, p-aminobenzoic acid, and an effective amount ofother vitamin compounds. The other vitamin compounds include vitamin A,vitamin D, vitamin E, vitamin K compounds and the like.

Promotion of gastrointestinal motility is used in a method for thetreatment of drug-induced gastrointestinal dysfunction (e.g.,opioid-induced, such as morphine-induced intestinal dysfunction orconstipation) in an object in need thereof. The method comprisesadministering a therapeutically effective amount of a combination of Bvitamins and C vitamins. Said object can be using opioid substances oropioids for post-surgical pain control or chronic pain control. Examplesof opioid substances and opioids include morphine, codeine, oxycodone,hydrocodone, methadone, fentanyl, and the combination thereof with ananti-inflammatory agent (such as acetaminophen or aspirin). In onepreferred embodiment, the composition comprising B vitamins and Cvitamins is a composition comprising vitamin B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, biotin, and vitamin C. In one more preferred embodiment, thecomposition comprising B vitamins and C vitamins is a compositioncomprising vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3(niacin), vitamin B5 (pantothenic acid), vitamin B6, folic acid, biotin,vitamin C, choline bitartrate, and inositol. In another more preferredembodiment, the composition comprising B vitamins and C vitamins is acomposition comprising vitamin B1 (thiamine), vitamin B2 (riboflavin),vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6, vitaminB12, folic acid, biotin, vitamin C, choline bitartrate, inositol, andp-aminobenzoic acid.

The promotion of gastrointestinal motility can be used to treatgastroparesis in an object in need thereof by administering atherapeutically effective amount of a combination of B vitamins and Cvitamins. In one preferred embodiment, the composition comprising Bvitamins and C vitamins is a composition comprising vitamin B1(thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, biotin, and vitamin C. In one morepreferred embodiment, the composition comprising B vitamins and Cvitamins is a composition comprising vitamin B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, folic acid, biotin, vitamin C, choline bitartrate, andinositol. In another more preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitaminC, choline bitartrate, inositol, and p-aminobenzoic acid.

In another embodiment, the promotion of gastrointestinal motility isused in a method for the treatment of a gastro esophageal reflux disease(GERD) in an object in need thereof. The method comprises administeringa therapeutically effective amount of a combination of B vitamins and Cvitamins. In one preferred embodiment, the composition comprising Bvitamins and C vitamins is a composition comprising vitamin B1(thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, biotin, and vitamin C. In one morepreferred embodiment, the composition comprising B vitamins and Cvitamins is a composition comprising vitamin B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, folic acid, biotin, vitamin C, choline bitartrate, andinositol. In another more preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitaminC, choline bitartrate, inositol, and p-aminobenzoic acid. In a specificembodiment, said gastro esophageal reflux disease is nighttime gastroesophageal reflux disease.

The invention also provides a method of promoting gastrointestinalmotility to treat the irritable bowel syndrome (IBS) in an object inneed thereof by administering a therapeutically effective amount of acombination of B vitamins and C vitamins. In one preferred embodiment,the composition comprising B vitamins and C vitamins is a compositioncomprising vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3,vitamin B5 (pantothenic acid), vitamin B6, biotin, and vitamin C. In onemore preferred embodiment, the composition comprising B vitamins and Cvitamins is a composition comprising vitamins B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, folic acid, biotin, vitamin C, choline bitartrate, andinositol. In another more preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitaminC, choline bitartrate, inositol, and para-aminobenzoic acid. Saidirritable bowel syndrome can be either a constipation-type irritablebowel syndrome or a constipation-and-diarrhea-alternating-type irritablebowel syndrome.

The invention also provides a method for treating constipation bypromoting gastrointestinal motility in an object in need thereof byadministering a therapeutically effective amount of a combination of Bvitamins and C vitamins. The constipation comprises functionalconstipation (caused by bad habits, dietary habits, senility, and othernon-organic pathology) and drug-induced constipation. In one preferredembodiment, the composition comprising B vitamins and C vitamins is acomposition comprising vitamin B1 (thiamine), vitamin B2 (riboflavin),vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6, biotin,and vitamin C. In one more preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitaminC, choline bitartrate, and inositol. In another more preferredembodiment, the composition comprising B vitamins and C vitamins is acomposition comprising vitamin B1 (thiamine), vitamin B2 (riboflavin),vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6, folicacid, biotin, vitamin C, choline bitartrate, inositol, andp-aminobenzoic acid.

In one embodiment, the promotion of gastrointestinal motility is used ina method for treatment of gastrointestinal dysfunction caused by orassociated with surgery (such as the slowdown of intestinal peristalsisafter operation) in an object in need thereof, the method comprisingadministering a therapeutically effective amount of a combination of Bvitamins and C vitamins. In one preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, biotin, and vitamin C. In one morepreferred embodiment, the composition comprising B vitamins and Cvitamins is a composition comprising vitamin B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, folic acid, biotin, vitamin C, choline bitartrate, andinositol. In another more preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitaminC, choline bitartrate, inositol, and p-aminobenzoic acid.

A preferred composition comprising B vitamins and C vitamins is acomposition comprising vitamin B1 (thiamine), vitamin B2 (riboflavin),vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6, biotin,and vitamin C. A more preferable composition comprising B vitamins and Cvitamins is a composition comprising vitamin B1 (thiamine), vitamin B2(riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),vitamin B6, folic acid, biotin, vitamin C, choline bitartrate, andinositol. In another more preferred embodiment, the compositioncomprising B vitamins and C vitamins is a composition comprising vitaminB1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5(pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitaminC, choline bitartrate, and p-aminobenzoic acid.

The dosage form of the composition comprising B vitamins and C vitaminsof the present invention can be, but not limited to a chewable tablet,various conventional adjuvants required for preparing different dosageforms can also be added to the composition of the present invention,such as disintegrants, lubricants, binders, antioxidants, complexingagents, and other pharmaceutical carriers to prepare by conventionalpreparation methods any of the commonly used oral dosage forms, such asdispersible tablets, granules, capsules, oral liquids, and other dosageforms.

The weight ratio of each component for the composition comprising Bvitamins and C vitamins in the present invention can have a plurality ofselections, and all of them have corresponding motility promotioneffects on the gastrointestinal system. In certain embodiments, it caninclude the following components based on weight ratio: 5-10 parts ofvitamin B1, 10-15 parts of vitamin B2, 6-25 parts of vitamin B3, 10-110parts of vitamin B5, 5-10 parts of vitamin B6, 0.01-0.1 parts of biotin,and 50-500 parts of vitamin C. In one preferred embodiment, the Bvitamins composition comprises the following components based on weightratio: 10 parts of vitamin B1, 15 parts of vitamin B2, 25 parts ofvitamin B3, 110 parts of vitamin B5, 10 parts of vitamin B6, 0.1 partsof biotin, and 150 parts of vitamin C. In one more preferred embodiment,the B vitamins composition comprises the following components based onweight ratio: 10 parts of vitamin B1, 15 parts of vitamin B2, 25 partsof vitamin B3, 110 parts of vitamin B5, 10 parts of vitamin B6, 0.1parts of biotin, 0.4 parts of folic acid, 250 parts of cholinebitartrate, 150 parts of vitamin C, and 250 parts of inositol. Inanother more preferred embodiment, the B vitamins composition comprisesthe following components based on weight ratio: 10 parts of vitamin B1,15 parts of vitamin B2, 25 parts of vitamin B3, 110 parts of vitamin B5,10 parts of vitamin B6, 0.1 parts of biotin, 0.4 parts of folic acid,250 parts of choline bitartrate, 0.025 parts of vitamin B12, and 150parts of vitamin C. In another more preferred embodiment, the B vitaminscomposition comprises the following components based on weight ratio: 10parts of vitamin B1, 15 parts of vitamin B2, 25 parts of vitamin B3, 110parts of vitamin B5, 10 parts of vitamin B6, 0.1 parts of biotin, 0.4parts of folic acid, 250 parts of choline bitartrate, 250 parts ofinositol, 0.025 parts of vitamin B12, 50 parts of p-aminobenzoic acid,and 150 parts of vitamin C.

B. Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of ordinary skillin the art to which this invention belongs. All patents, applications,published applications and other publications referred to herein areincorporated by reference in their entirety. If a definition set forthin this section is contrary to or otherwise inconsistent with adefinition set forth in the patents, applications, publishedapplications and other publications that are herein incorporated byreference, the definition set forth in this section prevails over thedefinition that is incorporated herein by reference.

As used herein, the singular forms “a”, “an”, and “the” mean “at leastone” or “one or more” unless the context clearly dictates otherwise.

The term “part,” particularly referring to a given quantity, refers to aquantity with a positive or negative deviation within 10%.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “contains,” “containing,” and any variations thereof, areintended to cover a non-exclusive inclusion, such that a process,method, product-by-process, or composition of matter that comprises,includes, or contains an element or list of elements does not includeonly those elements but can include other elements not expressly listedor inherent to such process, method, product-by-process, or compositionof matter.

As used herein, the term “B vitamins composition” includes all kinds ofvitamin B or their corresponding analogues or derivatives, for example,vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinicacid), vitamin B5 (pantothenic acid), vitamin B6 and so on.

As used herein, the terms “analogs” and “analogues” refers to any two ormore molecules or fragments that have roughly the same structure andhave the same biological activity but can have different levels ofactivity. The term “derivative” used herein refers to a more complexcompound derived from the replacement of a hydrogen atom or group ofatoms in a compound by other atoms or groups of atoms.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 : Changes of the small intestinal propulsive rate (%) of acharcoal solution in mice after drug administration.

FIG. 2 : The time of defecation of the first black stool after drugadministration.

FIG. 3 : The number of stools within 6 h after drug administration.

FIG. 4 : The wet stools weight within 6 h after drug administration.

FIG. 5 : The dry stools weight within 6 h after drug administration.

FIG. 6 : The water content of stools within 6 h after drugadministration.

FIG. 7 . Schematic diagram of the experimental method for the effect ofdifferent multivitamin BC prescriptions on small intestinal propulsiverate (%) of loperamide induced constipation mouse model.

FIG. 8 . Schematic diagram of the experimental method for the effect ofdifferent multivitamin BC prescriptions on defecation function ofloperamide induced constipation mouse model.

DETAILED DESCRIPTION Example 1: Effects of the Different Multivitamin BCPrescriptions on the Small Intestinal Propulsive Rate in Mice withLoperamide-Induced Constipation

1. Purpose of the Study

The purpose of this study was to evaluate the therapeutic effects ofdifferent prescriptions of multivitamin BC tablets in mice constipationmodel induced by loperamide.

2. Experimental Materials

2.1 Reagents and Instruments

Name Manufacturers Lot NO. Arabic gum Sinopharm Chemical F20111122Activated Tianjin Dingshengxin — carbon powder Chemical Co., Ltd. CMC-NaSinopharm Chemical 20160602 Tween 80 Sinopharm Chemical F20110615 Salinesolution Shandong Kangning A16031304 Pharmaceutical Co., Ltd. LoperamideSigma SLBG7320V Itopride Xiuzheng Pharmaceutical 150101 HydrochlorideGroup Tablets Analytical Shanghai Balance JA8002 balance InstrumentFactory2.2 Experimental AnimalsSpecies: mouseStrains: C57BL/6Gender and quantity: Male, 80Animal week-age: 6-8 weeksWeight range: 17.0-20.0 gAnimal sources: Shanghai Lingchang Biotechnology Co. LTDAnimal certificate number: 20130018201353. Experimental Design and Methods3.1 Test Grouping:

Experimental animals were randomly divided into 8 groups, 10-12 animalsper group by the random number table method. The doses and multivitaminBC tablets prescriptions for each groups are shown in Table 1 and Table2.

TABLE 1 Doses for each group of mice Intragastric Doses SubcutaneousGroups administration (mg/kg) injection Control 0.5% CMC-Na solution —1% Tween 80 in saline Model 0.5% CMC-Na solution — Loperamide solutionItopride Itopride suspension 153.75 Loperamide solution VBs* (5X) VBssuspension 523.512 Loperamide solution VBs + choline (5X) VBs + choline780.387 Loperamide suspension solution VBs + VC(5X) VBs + VC suspension677.637 Loperamide solution VBs + VC + biotin(5X) VBs + VC + biotin677.74 Loperamide suspension solution VBs + VC + choline VBs + VC +choline 934.512 Loperamide (5X) suspension solution *VBs: composition ofB vitamins

TABLE 2 Dose of each component of the multivitamin BC tablets EquivalentEquivalent dosage dosage Piece for mice for mice*5 NO. API (mg) (mg/kg)(mg/kg) 1 VB1 100 20.550 102.750 2 VB2 100 20.550 102.750 3 VB3 10020.550 102.750 4 VB6 100 20.550 102.750 5 Calcium 109 22.40 111.998pantothenate 6 Folic acid 0.4 0.082 0.411 7 VB12 0.1 0.021 0.103 8Choline 250 51.367 256.875 bitartrate 9 VC 150 30.825 154.125 10 Biotin0.1 0.0206 0.1033.2 Reagent Preparation

-   1) 0.5% CMC-Na solution: 2.0 g of CMC-Na powder was weighed and 300    ml ultra-pure water was slowly added thereto; the mixture was    subjected to magnetic stirring until it was completely dissolved to    reach a constant volume of 400 ml, thereby preparing a clear    solution of 0.5%, which was stored at 4° C. for later use.-   2) 1% Tween-80 in saline: 40 ml saline was accurately measured using    a measuring cylinder and added into a 50 ml centrifuge tube; 400 μl    Tween-80 was measured using a pipette and added into the centrifuge    tube; and the mixture was subjected to vortex oscillation to be    homogeneous and was then placed at room temperature for later use.-   3) 5% charcoal solution: 100 g of Arabic gum was accurately weighed    and 800 ml water was added thereto; and the solution was boiled    until it was transparent. 50 g of activated carbon powder was    weighed and added into the above solution and the mixture was boiled    for three times. After the solution was cool, water was added to    reach a constant volume of 1000 ml.-   4) Composition of B vitamins (5×): VB1, VB2, VB3, VB6, Calcium    pantothenate, Folic acid, VB12 and Biotin were accurately weighed    according to the “Equivalent dosage for mice (*5)” in table 2, then,    20 ml of 0.5% CMC-Na was added, and the mixture was subjected to    oscillation to become homogeneous, thereby forming a stable    suspension. This reagent was used immediately after it was prepared.-   5) Composition of B vitamins+Choline (5×): VB1, VB2, VB3, VB6,    Calcium pantothenate, Folic acid, VB12, Biotin and Choline    bitartrate were accurately weighed according to the “Equivalent    dosage for mice (*5)” in table 2, then, 20 ml of 0.5% CMC-Na was    added thereto, and the mixture was subjected to oscillation to    become homogeneous, thereby forming a stable suspension. This    reagent was used immediately after it was prepared.-   6) Composition of B vitamins+VC (5×): VB1, VB2, VB3, VB6, Calcium    pantothenate, Folic acid, VB12, Biotin and VC were accurately    weighed according to the “Equivalent dosage for mice (*5)” in table    2, then, 20 ml of 0.5% CMC-Na was added thereto, and the mixture was    subjected to oscillation to become homogeneous, thereby forming a    stable suspension. This reagent was used immediately after it was    prepared.-   7) Composition of B vitamins+VC+Biotin (5×): VB1, VB2, VB3, VB6,    Calcium pantothenate, Folic acid, VB12, VC and 3 parts of biotin    (0.3 mg of biotin/100 mg tablet) were accurately weighed according    to the “Equivalent dosage for mice (*5)” in table 2, then, 20 ml of    0.5% CMC-Na was added thereto, and the mixture was subjected to    oscillation to become homogeneous, thereby forming a stable    suspension. This reagent was used immediately after it was prepared.-   8) Composition of B vitamins+VC+Choline (5×): VB1, VB2, VB3, VB6,    Calcium pantothenate, Folic acid, VB12, Biotin, VC and Choline    bitartrate were accurately weighed according to the “Equivalent    dosage for mice (*5)” in table 2, then, 20 ml of 0.5% CMC-Na was    added thereto, and the mixture was subjected to oscillation to    become homogeneous, thereby forming a stable suspension. This    reagent was used immediately after it was prepared.-   9) Itopride Hydrochloride: after grinding of 2 tablets itopride    hydrochloride, 13 ml of 0.5% CMC-Na was added thereto, and the    mixture was subjected to oscillation to become homogeneous, thereby    forming a stable suspension. This reagent was used immediately after    it was prepared.-   10) Loperamide: 5.0 mg of loperamide was accurately weighed and 20    ml of a saline solution with 1.0% Tween 80 was added thereto; after    being subjected to oscillation to become homogeneous, the mixture    was subjected to ultrasound for at least 5 minutes. This reagent was    used immediately after it was prepared.    3.3 Test Methods

After fasting and freely drinking for about 22-24 hours, each group ofthe mice were administrated at above doses at 20 ml/kg, and the modelgroup and the control group were intragastrically administrated with0.5% CMC-Na solution at the same dose. After 30 minutes ofadministration, the control group was injected subcutaneously with thesaline solution containing 1.0% Tween 80 while the other groups wereinjected subcutaneously with loperamide in an injection volume of 10ml/kg. After a subcutaneous injection for 30 minutes, an intragastricadministration of the charcoal solution was performed at anadministration volume of 10 ml/kg.

3.4 Observation IndexSmall intestinal propulsive rate (%)=(the propulsive distance of thecharcoal solution/the total length of the small intestine)×100

Twenty minutes after an intragastric administration of the charcoalsolution, the animal was sacrificed by cervical dislocation and itsabdominal cavity was immediately opened to separate the mesentery. Theintestinal canal from the pylorus to the ileocecal junction wascarefully removed and put on a tray. Be careful not to involve the smallintestine, gently place the small intestine in a straight line, andmeasure the total length of the small intestine. The length from thepylorus to the front of the charcoal solution is the propulsive distanceof the charcoal solution, and the small intestinal propulsive rate (%)of the charcoal solution was calculated.

3.5 Data Analysis

Experimental data were expressed by Mean±SE and one-way ANOVA wasperformed by SPSS. Comparison between groups was made using LSD test.

4 Test Results

Effects of the different multivitamin BC tablets prescriptions on thesmall intestinal propulsive distance and propulsive rate (%) of thecharcoal solution in the mice are shown in Table 3 and FIG. 1 .

TABLE 3 Effects of the different multivitamin BC tablets prescriptionson the small intestinal propulsive rate in mice with loperamide-inducedconstipation (Mean ± SD) Propulsive Small Length of distance ofintestinal Animal Animal the small the charcoal propulsive number weightintestine solution rate Groups (n) (g) (cm) (cm) (%) Control 10 17.4 ±0.7 18.8 ± 2.6 12.0 ± 1.4*** 64.5 ± 8.5*** Model 10 18.0 ± 0.6 19.6 ±2.3 5.5 ± 1.2  28.1 ± 5.3   Itopride 10 17.2 ± 0.6 20.7 ± 2.0 8.8 ±1.2** 42.7 ± 5.5*** VBs (5X) 12 17.3 ± 0.9 20.9 ± 2.2  9.0 ± 2.9*** 42.7 ± 12.4*** VBs + choline 12 17.4 ± 0.6 21.0 ± 2.2  9.5 ± 2.0***45.2 ± 8.0*** (5X) VBs + VC (5X) 12 17.4 ± 0.7 21.3 ± 2.1  9.5 ± 2.1***43.0 ± 8.2*** VBs + VC + biotin 12 17.2 ± 0.6 21.9 ± 1.9 8.7 ± 1.1**40.1 ± 6.5**  (5X) VBs + VC + 12 17.1 ± 0.8 21.6 ± 2.5 11.3 ± 2.3***52.1 ± 6.8*** choline (5X) *vs model group, P < 0.05; **vs model group,P < 0.01, ***vs model group, P < 0.00l

The results showed that compared with the control group, the smallintestinal propulsive rate (%) of the model group was significantlyreduced (64.5±8.5 VS 28.1±5.3), indicating that the mouse constipationmodel was successfully prepared. Compared with model group, the smallintestinal propulsive rate (%) were improved at different levels inItopride positive control group, VBs (5×), VBs+choline (5×), VBs+VC(5×), VBs+VC+biotin (5×), VBs+VC+choline (5×) groups (28.1±5.3 VS42.7±5.5, 42.7±12 0.4, 45 0.2±8.0, 43.0±8.2, 40.1±6.5, 52.1±6.8).

5. Conclusion

All the different multivitamin BC tablets prescriptions can improvesmall intestinal propulsive rate (%) of the 2.5 mg/kg loperamide-inducedconstipation mouse model, and the effects of VBs (5×), VBs+choline (5×),VBs+VC (5×), VBs+VC+biotin (5×), VBs+VC+choline (5×) groups weresuperior to Itopride positive control group.

Example 2: Effects of the Different Multivitamin BC TabletsPrescriptions on the Defecate Function in Mice with Loperamide-InducedConstipation

1. Purpose of the Study

The purpose of this study was to evaluate the therapeutic effects ofdifferent prescriptions of multivitamin BC tablets in mice constipationmodel induced by loperamide.

2. Experimental Materials

2.1 Reagents and Instruments

Name Manufacturers Lot NO. Arabic gum Sinopharm Chemical F20111122Activated carbon Tianjin Dingshengxin — Chemical Co., Ltd. powder CMC-NaSinopharm Chemical 20160602 Tween 80 Sinopharm Chemical F20110615 Salinesolution Shandong Kangning A16031304 Pharmaceutical Co., Ltd. LoperamideSigma SLBG7320V Analytical balance Shanghai Balance JA8002 InstrumentFactory2.2 Experimental AnimalsSpecies: mouseStrains: C57BL/6Gender and quantity: Female, 40Animal week-age: 6-8 weeksWeight range: 22.0-27.0 gAnimal sources: Shanghai Lingchang Biotechnology Co. LTDAnimal certificate number: 20130018204763. Experimental Design and Methods3.1 Test Grouping:

Experimental animals were randomly divided into 8 groups, 5 animals pergroup by the random number table method. The doses and differentmultivitamin BC tablets prescriptions for each groups are shown in Table4 and Table 5.

TABLE 4 Doses for each group of mice Intragastric Doses SubcutaneousGroups administration (mg/kg) injection Control 0.5% CMC-Na solution —1% Tween 80 in saline Model 0.5% CMC-Na solution — Loperamide solutionVBs (5X) VBs suspension 523.512 Loperamide solution VBs + choline (5X)VBs + choline 780.387 Loperamide suspension solution VBs + VC(5X) VBs +VC suspension 677.637 Loperamide solution VBs + VC + biotin(5X) VBs +VC + biotin 677.74 Loperamide suspension solution VBs + VC + choline(5X) VBs + VC + choline 934.512 Loperamide suspension solution

TABLE 5 Dose of each component of the multivitamin BC tablets EquivalentEquivalent dosage dosage Piece for mice for mice*5 NO. API (mg) (mg/kg)(mg/kg) 1 VB1 100 20.550 102.750 2 VB2 100 20.550 102.750 3 VB3 10020.550 102.750 4 VB6 100 20.550 102.750 5 Calcium 109 22.40 111.998pantothenate 6 Folic acid 0.4 0.082 0.411 7 VB12 0.1 0.021 0.103 8Choline 250 51.367 256.875 bitartrate 9 VC 150 30.825 154.125 10 Biotin0.1 0.0206 0.1033.2 Reagent Preparation

-   1) 0.5% CMC-Na solution: 2.0 g of CMC-Na powder was weighed and 300    ml ultra-pure water was slowly added thereto; the mixture was    subjected to magnetic stirring until it was completely dissolved to    reach a constant volume of 400 ml, thereby preparing a clear    solution of 0.5%, which was stored at 4° C. for later use.-   2) 1% Tween-80 in saline: 40 ml saline was accurately measured using    a measuring cylinder and added into a 50 ml centrifuge tube; 400 μl    Tween-80 was measured using a pipette and added into the centrifuge    tube; and the mixture was subjected to vortex oscillation to be    homogeneous and was then placed at room temperature for later use.-   3) 5% charcoal solution: 100 g of Arabic gum was accurately weighed    and 800 ml water was added thereto; and the solution was boiled    until it was transparent. 50 g of activated carbon powder was    weighed and added into the above solution and the mixture was boiled    for three times. After the solution was cool, water was added to    reach a constant volume of 1000 ml.-   4) Composition of B vitamins (5×): VB1    VB2    VB3    VB6    Calcium pantothenate    Folic acid    VB12 and Biotin were accurately weighed according to the “Equivalent    dosage for mice (*5)” in table 5, then, 20 ml of 0.5% CMC-Na was    added, and the mixture was subjected to oscillation to become    homogeneous, thereby forming a stable suspension. This reagent was    used immediately after it was prepared.-   5) Composition of B vitamins+Choline (5×): VB1    VB2    VB3    VB6    Calcium pantothenate, Folic acid, VB12, Biotin and Choline    bitartrate were accurately weighed according to the “Equivalent    dosage for mice (*5)” in table 5, then, 20 ml of 0.5% CMC-Na was    added thereto, and the mixture was subjected to oscillation to    become homogeneous, thereby forming a stable suspension. This    reagent was used immediately after it was prepared.-   6) Composition of B vitamins+VC (5×): VB1    VB2    VB3    VB6    Calcium pantothenate    Folic acid    VB12    Biotin and VC were accurately weighed according to the “Equivalent    dosage for mice (*5)” in table 5, then, 20 ml of 0.5% CMC-Na was    added thereto, and the mixture was subjected to oscillation to    become homogeneous, thereby forming a stable suspension. This    reagent was used immediately after it was prepared.-   7) Composition of B vitamins+VC+Biotin (5×): VB1    VB2    VB3    VB6    Calcium pantothenate    Folic acid    VB12    VC and 3 parts of biotin (0.3 mg of biotin/100 mg tablet) were    accurately weighed according to the “Equivalent dosage for mice    (*5)” in table 5, then, 20 ml of 0.5% CMC-Na was added thereto, and    the mixture was subjected to oscillation to become homogeneous,    thereby forming a stable suspension. This reagent was used    immediately after it was prepared.-   8) Composition of B vitamins+VC+Choline (5×): VB1    VB2    VB3    VB6    Calcium pantothenate    Folic acid    VB12    Biotin    VC and Choline bitartrate were accurately weighed according to the    “Equivalent dosage for mice (*5)” in table 5, then, 20 ml of 0.5%    CMC-Na was added thereto, and the mixture was subjected to    oscillation to become homogeneous, thereby forming a stable    suspension. This reagent was used immediately after it was prepared.-   9) Loperamide: 5.0 mg of loperamide was accurately weighed and 20 ml    of a saline solution with 1.0% Tween 80 was added thereto; after    being subjected to oscillation to become homogeneous, the mixture    was subjected to ultrasound for at least 5 minutes. This reagent was    used immediately after it was prepared.    3.3 Test Methods

Free access to forage and drinking water was allowed. Each group of themice were administrated at above doses at 20 ml/kg, and the model groupand the control group were intragastrically administrated with 0.5%CMC-Na solution at the same dose. After 30 minutes of administration,the control group was injected subcutaneously with the saline solutioncontaining 1.0% Tween 80 while the other groups were injectedsubcutaneously with loperamide in an injection volume of 10 ml/kg. Aftera subcutaneous injection for 30 minutes, an intragastric administrationof the charcoal solution was performed at an administration volume of 10ml/kg. Start time counting 15 mins after feeding charcoal, recorded thetime of defecation of first black stool, the number of stools between0-2 h and 4-6 h, weighing and measuring the dry weight (60° C., 6 h) ofstools. Then calculated the stools water content (%)[(the wet stoolweight−the dry stool weight)/(the wet stool weight)*100%]. Each mice wasraised in a single cage during the experiment, fasted but without waterdeprivation. The weight of each mice was recorded before drugadministration and at the end of the study, respectively.

3.4 Observation Index

Start time counting 15 mins after feeding charcoal, recorded the time ofdefecation of first black stool, the number of stools between 0-2 h, 2-4h, 4-6 h respectively, weighing and measuring the dry stool weight (60°C., 6 h). Then calculated the stool water content (%)[(the wet stoolweight−the dry stool weight)/(the wet stool weight)*100%]. Each mice wasraised in a single cage during the experiment, fasted but without waterdeprivation. The weight of each mice was recorded before drugadministration and at the end of the study, respectively.

3.5 Data Analysis

Experimental data were expressed by Mean±SE and one-way ANOVA wasperformed by SPSS. Comparison between groups was made using LSD test.

4 Test Results

Effects of the different multivitamin BC tablets prescriptions on thetime of defecation of first black stool, the number of stools within 6 hwere shown in Table 6 and FIG. 2, 3 .

Effects of the different multivitamin BC tablets prescriptions on micewet stool weight, dry stool weight and the stool water content within 6h showed in Table 7, and FIG. 4, 5, 6 .

TABLE 6 Effects of the different multivitamin BC tablets prescriptionson the time of defecation of first black stool, the number of stoolswithin 6 h in loperamide-induced constipation mouse (Mean ± SE). Thetime of defecation The number of the first of stools Weight black stoolwithin 6 h Groups (g) (min) (grain) Control 25.08 ± 0.30 104.0 ± 12.00 14.6 ± 4.51  Model 24.58 ± 0.59 264.2 ± 131.18 2.8 ± 1.92 VBs (5X) 25.40± 0.77 177.2 ± 105.25 6.6 ± 3.44 VBs + choline (5X) 25.58 ± 0.73 335.2 ±55.45  4.8 ± 2.86 VBs + VC(5X) 24.66 ± 0.73 178.8 ± 113.19 2.0 ± 1.22VBs + VC + biotin 24.34 ± 1.25 282.6 ± 115.66 2.8 ± 1.64 (5X) VBs + VC +choline 24.98 ± 0.85 171.4 ± 123.03 3.2 ± 1.30 (5X)

TABLE 7 Effects of the different multivitamin BC tablets prescriptionson mice wet stool weight, dry stool weight and the stool water contentwithin 6 h in mice with loperamide-induced constipation (Mean ± SE). Thewet The dry stool weight stool weight The fecal within 6 h within 6 hwater content Groups (g) (g) (%) Control 0.169 ± 0.024 0.100 ± 0.02339.17 ± 17.12 Model 0.043 ± 0.031 0.0246 ± 0.019  31.59 ± 25.82 VBs (5X)0.092 ± 0.040 0.0567 ± 0.023  37.19 ± 8.94  VBs + choline (5X) 0.068 ±0.048 0.046 ± 0.031 25.43 ± 14.61 VBs + VC(5X) 0.038 ± 0.030 0.021 ±0.017 36.56 ± 25.03 VBs + VC + biotin(5X) 0.059 ± 0.042 0.026 ± 0.01450.95 ± 10.53 VBs + VC + choline 0.054 ± 0.023 0.032 ± 0.015 38.31 ±18.37 (5X)

The results showed that compared with the control group, the time ofdefecation of the first black stool of the model group extended(264.2±131.18 VS 104.0±12.00). Compared with model group, the time ofdefecation of the first black stool in VBs (5×), VBs+VC (5×),VBs+VC+biotin (5×), VBs+VC+ choline (5×) groups were shorten to acertain degree (264.2±131.18 VS 177.2±105.25, 178.8±113.19,171.4±123.03).

Compared with the control group, the number of stools, the wet stoolweight, the dry stool weight within 6 h were all decreased in modelgroup slightly. The number of stools in VBs (5×), VBs+choline (5×),VBs+VC+choline (5×) groups were higher than the model group (2.8±1.92 VS6.6±3.44, 4.8±2.86, 3.2±1.30). The wet stool weight of VBs (5×),VBs+choline (5×), VBs+VC+biotin (5×), VBs+VC+choline (5×) groups weregreater than the model group (0.043±0.031 VS 0.092±0.040, 0.068±0.048,0.059±0.042, 0.054±0.023). The dry stool weight of VBs (5×), VBs+choline(5×), VBs+VC+biotin (5×), VBs+VC+choline (5×) groups were greater thanthe model group (0.0246±0.019 VS 0.0567±0.023, 0.046±0.031, 0.026±0.014,0.032±0.015). The stool water content of VBs (5×), VBs+VC (5×),VBs+VC+biotin (5×), VBs+VC+choline (5×) groups were slightly higher thanthe model group (31.59±25.82 VS 37.19±8.94, 36.56±25.03, 50.95±10.53,38.31±18.37).

5. Conclusion

Different multivitamin BC tablets prescriptions improved the defecationfunctions in the 2.5 mg/kg loperamide-induced constipation mouse model.

In order to describe and understand the present invention more clearly,we describe the present invention by examples in detail. It is clearthat modification and alterations of the present invention will beapparent to those skilled in the art without departing from the scopeand spirit of the present invention.

What is claimed is:
 1. A method for treating a condition or diseaseassociated with insufficient gastrointestinal system motility in asubject in need thereof, comprising administering a compositioncomprising B vitamins and C vitamins to the subject, wherein thecomposition comprising B vitamins and C vitamins comprises the followingcomponents based on weight ratio: 100 parts of vitamin B1, 100 parts ofvitamin B2, 100 parts of vitamin B3, 100 parts of vitamin B6, 109 partsof vitamin B5, 0.4 parts of folic acid, 0.1 parts of vitamin B12, 0.1parts of biotin and 150 parts of vitamin C.
 2. A method for treating acondition or disease associated with insufficient gastrointestinalsystem motility in a subject in need thereof, comprising administering acomposition comprising B vitamins and C vitamins to the subject, whereinthe composition comprising B vitamins and C vitamins comprises thefollowing components based on weight ratio: 100 parts of vitamin B1, 100parts of vitamin B2, 100 parts of vitamin B3, 100 parts of vitamin B6,109 parts of vitamin B5, 0.4 parts of folic acid, 0.1 parts of vitaminB12, 0.3 parts of biotin and 150 parts of vitamin C.
 3. A method fortreating a condition or disease associated with insufficientgastrointestinal system motility in a subject in need thereof,comprising administering a composition comprising B vitamins and Cvitamins to the subject, wherein the composition comprising B vitaminsand C vitamins comprises the following components based on weight ratio:100 parts of vitamin B1, 100 parts of vitamin B2, 100 parts of vitaminB3, 100 parts of vitamin B6, 109 parts of vitamin B5, 0.4 parts of folicacid, 0.1 parts of vitamin B12, 0.1 parts of biotin and 250 parts ofcholine bitartrate.
 4. The method of claim 1, wherein the compositionfurther comprises inositol and p-aminobenzoic acid.
 5. The method ofclaim 2, wherein the composition further comprises inositol andp-aminobenzoic acid.
 6. The method of claim 3, wherein the compositionfurther comprises inositol and p-aminobenzoic acid.
 7. The method ofclaim 1, wherein the vitamin B1 is thiamine, the vitamin B2 isriboflavin, the vitamin B3 is niacin, the vitamin B5 is pantothenic acidor calcium pantothenate, and the vitamin C is selected from the groupconsisting of L-ascorbic acid, L sodium ascorbate, magnesium ascorbylphosphate, L-Ascorbate-polyphosphate, ascorbyl palmitate, and ascorbinstearate.
 8. The method of claim 2, wherein the vitamin B1 is thiamine,the vitamin B2 is riboflavin, the vitamin B3 is niacin, the vitamin B5is pantothenic acid or calcium pantothenate, and the vitamin C isselected from the group consisting of L-ascorbic acid, L sodiumascorbate, magnesium ascorbyl phosphate, L-Ascorbate-polyphosphate,ascorbyl palmitate, and ascorbin stearate.
 9. The method of claim 3,wherein the vitamin B1 is thiamine, the vitamin B2 is riboflavin, thevitamin B3 is niacin, the vitamin B5 is pantothenic acid or calciumpantothenate, and the vitamin C is selected from the group consisting ofL-ascorbic acid, L sodium ascorbate, magnesium ascorbyl phosphate,L-Ascorbate-polyphosphate, ascorbyl palmitate, and ascorbin stearate.10. The method of claim 4, wherein the vitamin B1 is thiamine, thevitamin B2 is riboflavin, the vitamin B3 is niacin, the vitamin B5 ispantothenic acid or calcium pantothenate, and the vitamin C is selectedfrom the group consisting of L-ascorbic acid, L sodium ascorbate,magnesium ascorbyl phosphate, L-Ascorbate-polyphosphate, ascorbylpalmitate, and ascorbin stearate.
 11. The method of claim 5, wherein thevitamin B1 is thiamine, the vitamin B2 is riboflavin, the vitamin B3 isniacin, the vitamin B5 is pantothenic acid or calcium pantothenate, andthe vitamin C is selected from the group consisting of L-ascorbic acid,L sodium ascorbate, magnesium ascorbyl phosphate,L-Ascorbate-polyphosphate, ascorbyl palmitate, and ascorbin stearate.12. The method of claim 6, wherein the vitamin B1 is thiamine, thevitamin B2 is riboflavin, the vitamin B3 is niacin, the vitamin B5 ispantothenic acid or calcium pantothenate, and the vitamin C is selectedfrom the group consisting of L-ascorbic acid, L sodium ascorbate,magnesium ascorbyl phosphate, L-Ascorbate-polyphosphate, ascorbylpalmitate, and ascorbin stearate.
 13. A composition in an oral dosageform for treating a condition or disease associated with insufficientgastrointestinal system motility in a subject in need thereof, whereinthe composition comprises the following components based on weightratio: 100 parts of vitamin B1, 100 parts of vitamin B2, 100 parts ofvitamin B3, 100 parts of vitamin B6, 109 parts of vitamin B5, 0.4 partsof folic acid, 0.1 parts of vitamin B12, 0.1 parts of biotin and 150parts of vitamin C.
 14. The composition of claim 13, wherein the oraldosage form is a chewable tablet.
 15. The composition of claim 13,wherein the oral dosage form is an oral liquid.
 16. The composition ofclaim 13, wherein the oral dosage form is a capsule.
 17. The compositionof claim 13, wherein the vitamin B1 is thiamine, the vitamin B2 isriboflavin, the vitamin B3 is niacin, the vitamin B5 is pantothenic acidor calcium pantothenate, and the vitamin C is selected from the groupconsisting of L-ascorbic acid, L sodium ascorbate, magnesium ascorbylphosphate, L-Ascorbate-polyphosphate, ascorbyl palmitate, and ascorbinstearate.